The overall objective of the research being carried out in this laboratory is to learn more about the possible role of oxygen in local regulation of blood flow. It has already been shown that contractile function of isolated vascular smooth muscle is affected by local variations in oxygen pressure. The mechanism(s) for this effect and its significance in blood flow regulation in the intact vascular bed remain to be clarified. Hence, the specific aim of this research proposal is to determine whether or not this sensitivity to oxygen is related to the role of oxygen in electron transport within the mitochondria of the vascular smooth muscle cells. To accomplish this aim, the exact relationships among contractile function, local oxygen pressure and respiratory chain function (oxidative metabolism) will be studied using isolated perfused small arteries and arterioles from cardiac and skeletal muscle of rabbits, other animal species and humans. Vascular tone (measured by recording constant-flow perfusion pressure of constant-pressure vessel radius), localized oxygen pressure (measured by microfluorometric and microelectrode techniques), and the oxidation-reduction state of Nicotinamide-Adenine Dinucleotide (NAD) in the respiratory chain (measured by a microfluorometric technique) will be measured simultaneously at various oxygen pressures. If it is shown that reduction of the respiratory chain occurs at the same or higher oxygen pressures than does depression of vascular tone, the relationship between oxygen and vascular tone could be explained by a metabolic hypothesis. If, on the other hand, the chain becomes reduced at oxygen pressures significantly less than does depression tone, this relationship could be explained by a non-metabolic hypothesis. The knowledge of which of these hypotheses is correct will be important in assessing the in vivo significance of the observations obtained in vitro.